This application seeks support for a Renewed Program Project of research into the physical-chemical mechanisms of cell membrane function: electrical excitation and chemical transport. Investigators employ model systems ranging from the synthetic lipid bilayer membrane through the erythrocyte membrane to the complex level of membrane functioning in synthetic preparations of cardiac muscle. Fundamental investigations are directed to 1) the quantitative description of the voltage-dependent conductances in a natural membrane (cardiac cell membrane), 2) the synthesis of voltage-dependent conductances in lipid bilayer membranes to determine the physical-chemical nature of such conductance changes, 3) the study of the thermodynamic properties of membranes to determine the molecular mechanisms of membrane transport, 4) the study of membrane antigens associated with active cation transport as they express activity and conformation. Methods of studying membrane properties include: current/voltage-clamp analysis of membrane conductances, voltage/current noise measurements, ion fluxes (radioactive tracer measurements), immunological methods, partition coefficients, calorimetric measurements, electron microscopy as well as theoretical modelling. Novel techniques include: the combination of tissue culture and immunological techniques to the growth of synthetic preparations of cardiac muscle with specific geometries and membrane properties, the technique of membrane fusion using phospholipid vesicles to introduce cell membrane proteins into planar lipid bilayers, foreign substances into cells, and to create extraordinarily large cells.